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Title: Molecular and cellular expression of novel genes associated with breast cancer
Author: Laversin, Stephanie Anne Sophie
ISNI:       0000 0004 2678 2194
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2009
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An improved and individualised breast cancer care can be pursued with the use of tumour markers that are associated with risk assessment, diagnosis, prognosis, prediction of treatment outcome, monitoring of the disease and development of novel therapies. As such, this study proposed to characterise and evaluate the potential for the management of breast cancer of four novel unpublished breast-associated genes, the breast-associated UniGene clusters (BUC6, BUC9, BUC10 and BUC11), which were identified in our laboratory by database mining. The first aspect of this research project was to undertake extensive in silico analysis and in vitro expression analysis for all genes using sequencing and RT-PCR based assays on a variety of tissues of normal and cancerous origin in order to further select the most promising candidates for potential use in cancer care. In light of all the data collected, the work was subsequently focused on the BUC11 gene. SinceBUC11 mRNA was found to be expressed at very low levels in normal tissues except in some non-essential tissues where it is expressed at a higher level, BUC11 was not considered a cancer testis antigen. BUC11 mRNA was also found at high levels in all testicular cancer tissues tested as well as in a quarter of prostate cancer tissues tested and at lower levels in a small proportion of melanomas, and thus BUC11 was not considered to be a tumour-specific gene. Quantitative RT-PCR analysis of a large panel of normal/cancer breast tissues has demonstrated that up to 97% of all tissues expressed BUC11 mRNA and 60.6% of patients over-expressed BUC11 mRNA. Immunoassays performed with thecustom-made anti-BUC11 antibody showed that BUC11 protein was preferentially found in the epithelial luminal type of malignant breast cells however no evidence was found to link BUC11 protein with breast tumour formation, state or progression of the disease. Therefore, the study also aimed to elucidate the molecular pathways that BUC11 may be involved in. Using a combination of in vitro gene silencing/induction based experiments and gene chip microarray technology, BUC11 was shown to potentially have a function in pathways controlling the proliferation of cells. The data obtained on the BUC11 geneduring the course of this study provided a rationale to further investigate the potential immunogenicity of its protein in a transgenic mouse model however preliminary experiments did not lead to any conclusive data. Collectively, this study demonstrated the expression analysis of a novel gene set which can potentially have clinical utility for several cancers, especially the most promising candidate BUC11, and which require further investigation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available